Navigating Carrier Screening

Carrier screening is a blood or saliva test offered to individuals of reproductive age, usually pregnant women, to assess if they are a carrier of certain conditions. For some conditions, like cystic fibrosis, male partners (or donor sperm) would also have to be a carrier in order for there to be concern for future or current pregnancies. If both members of a couple are carriers, then there is a 25% chance that each pregnancy they conceive would have the condition. If a someone whose genetically female is found to be a carrier of an x-linked condition, then there is a 50% chance for her sons to have the condition and a 50% chance her daughters would also be carriers. Sometimes, carriers of x-linked conditions can have symptoms of the condition as well.

Not everyone desires this information because of the implications the knowledge can have on future pregnancies. Someone may not want to know there is a 25% chance for their future baby to have a genetic condition, when there is a 75% chance that their baby would not. This kind of knowledge may cause undue stress, and the person would not want to consider things such as prenatal testing or preimplantation genetic testing. They would prefer to do things the classic way, where people had babies and didn’t do all the additional testing.

Other times, people feel the information would empower them and help them consider different ways of conception such as in vitro fertilization (IVF) with preimplantation genetic testing (PGT) for the condition. IVF with PGT is available in order to avoid conceiving a pregnancy with the condition. They may know that they could not take care of a child with a genetic condition, and consider options such as termination or adoption if they were already pregnant. In some cases, people are just provided with reassurance that they aren’t carriers. 

If someone decides carrier screening is the right test for them, then it is important they speak to a specialist, such as a genetic counselor, to discuss the screening options. Unfortunately, carrier screening is not as straightforward as it should be. There are multiple types of tests and laboratories that offer carrier screening. So, how can someone navigate it all?

Start with what conditions to test for.

The American College of Obstetrics and Gynecology states everyone should be offered cystic fibrosis and spinal muscular atrophy carrier screening because those conditions are most often seen in the general population.

Sickle cell disease and conditions like it called hemoglobinopathies are recommended for people with African, Mediterranean, Southeast Asian, Middle Eastern, or West Indian ancestry. Carrier screening for hemoglobinopathies is also offered to people who have had a complete blood count and their Mean Corpuscular Volume (MCV) or Mean Corpuscular Hemoglobin (MCH) are low. MCV and MCH are values that provide information on the number of hemoglobin someone has in their bloodstream and red blood cell size.

Tay Sachs, Canavan, Cystic Fibrosis, and Familial Dysautonomia are offered to those with Ashkenazi Jewish ancestry. People can choose to be screened for conditions based on their ancestry. 

There is also the option to be screened for 200 conditions or more through testing called “expanded carrier screening”. Expanded carrier screening usually include the conditions above but also many other conditions.  The types of conditions on the panel range on severity and availability of treatment. 

Usually, if someone is tested for over 200 conditions, the screen comes back positive for at least one condition. This is to be expected given we are all carriers of at least some genetic conditions. However, as a carrier, we usually have no signs of the condition, so we are never aware of our carrier status until we do testing. Additionally, for many of the conditions on the panel, they are are ones that both partners need to be a carrier of before there are risks to a future pregnancies. However, there are nuances to carrier screening.

Once it is decided which conditions to test for, the lab and methodology needs to be chosen.

Not all labs offer the same carrier screening panel, and they do not test for those conditions the same way. This is where it can get tricky. A quick refresher on genes is helpful for this part, stick with me!

Remember our genes are like an instructional manual for our bodies, telling our bodies how to grow and develop. One gene is like a page from that instruction manual. When carrier screening is performed, it looks at specific genes. This is like going to one page of that manual and reading through it to see if there are any words that are misspelled or missing. If that occurs, then that page of instructions might not be understandable and the body isn't able to carry out the function of that gene as it is supposed to. Similarly, when carrier screening is performed, the gene of interest is “read” over to see if there are errors to it that cause the gene not to work and the body unable to carry out the intended function of that gene.

Some labs will go to those pages of the instruction manual and only look at the most common errors that can occur. What scientists have found is that for a lot of genes, they do not work for the same reason. For example, cystic fibrosis is caused by both copies of the CFTR gene not working properly. CFTR is a large gene and there are many mutations or errors that can occur to cause the gene to no longer work properly. There are over 1000 different errors that can occur. However, some labs may only test for 32 of the errors or mutations because they are the most common ones. This is called mutation analysis and can be an effective and cost conscious way to determine if someone is a carrier. How scientists determined which mutations were the most common was by looking at specific data collections of people. Typically, these data pools are of people with Ashkenazi Jewish or European ancestry, so mutation analysis may not be as helpful for individuals with other backgrounds because it may be more likely they are carriers of other mutations.

Other labs will look at all the known reasons that the gene might not be working properly. Essentially, the entire page for that gene is read, line by line, and checked for any errors. This is called sequencing of the gene and is more likely to identify someone as a carrier, if they truly are one. 

However, despite gene sequencing or mutation analysis, there is always a residual chance someone could be a carrier even if their carrier screening is negative. With gene sequencing, this residual chance is usually lower than mutation analysis. 

When you are undergoing carrier screening, the questions to ask are:

• What conditions do you want to be screened for?

• Does the lab perform mutation analysis or gene sequencing?

• If your test comes back negative, then what is your residual risk to be a carrier?

• Do you and your partner want to have carrier screening at the same time or do you want to wait to see what conditions you are a carrier of first and test him or her based on that information?

Navigating carrier screening can be difficult. This is why talking with a genetic counselor can be helpful to make sure you are getting the kind of screening you desire. Find a genetic counselor here: https://www.nsgc.org/page/student_physician-contact. 

* This blog constitutes general information about genetic testing and medical screening. This blog does not offer or provide medical advice or diagnosis, and nothing in this blog/webinar should be construed as medical advice or diagnosis. Do not rely on the information in this blog/webinar to make medical management decisions. Please consult with a medical professional before making those decisions. Do not delay in seeking professional medical advice if you think you have a medical concern. Do not disregard professional medical advice based on any information received in this blog.